A PHARMACOKINETIC ANALYSIS OF AMPICILLIN IN THE CEREBROSPINAL FLUID OF RABBITS WITH STAPHYLOCOCCAL MENINGITIS

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Ampicillin demonstrates a potent bactericidal activity against the common pathogens: Haemophilus influenzae (except for those strains that produce beta-lactamase), Neisseria meningitidis, group A and B Streptococcus, Streptococcus pneumoniae, Listeria, Enterococcus, Proteus mirabilis and Escherichia coli, and has received a wide acceptance as a single antibiotic regimen in the treatment of bacterial meningitis caused by the above organism. Although concentrations of an antibiotic in serum are commonly correlated with the degree of therapeutic effectiveness in systemic infections, cerebrospinal fluid (CSF) concentrations should serve as a therapeutic guide in the case of bacterial meningitis, However, bacterial meningitis is one of the diseases in which therapeutic concentrations of antibiotics are difficult to attain at the site of infections because of the action of blood-CSF barrier. In the treatment of bacterial meningitis, although intravenous administrations of antibiotics are known to be superior to their intramuscular in jections, little published data discussing the duration of intravenous infusion of drugs are available.As ampicillin is the main drug for the treatment of bacterial meningitis, it is chosen as a subject in this study.
The present study was designed to determine the pharmacokinetic differences in CSF between 60 minutes continuous and bolus intravenous administrations of ampicillin by analysing the pharmacokinetic indices such as half-lives (T1/2), maximum concentrations (C_max), the time when C_max was obtained (T_max), and the area-under-the-serum or CSF concentration-time curve (AUC), using a serial sampling method from an individual rabbit with staphylococcal meningitis.